1. Cell Biology
  2. Chromosomes and Gene Expression

Mitotic chromosomes scale to nuclear-cytoplasmic ratio and cell size in Xenopus

  1. Coral Y Zhou  Is a corresponding author
  2. Bastiaan Dekker
  3. Ziyuan Liu
  4. Hilda Cabrera
  5. Joel Ryan
  6. Job Dekker
  7. Rebecca Heald  Is a corresponding author
  1. University of California, Berkeley, United States
  2. University of Massachusetts Medical School, United States
  3. McGill University, Canada
https://doi.org/10.7554/eLife.84360
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  1. Coral Y Zhou
  2. Bastiaan Dekker
  3. Ziyuan Liu
  4. Hilda Cabrera
  5. Joel Ryan
  6. Job Dekker
  7. Rebecca Heald
(2023)
Mitotic chromosomes scale to nuclear-cytoplasmic ratio and cell size in Xenopus
eLife 12:e84360.
https://doi.org/10.7554/eLife.84360
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Abstract

During the rapid and reductive cleavage divisions of early embryogenesis, subcellular structures such as the nucleus and mitotic spindle scale to decreasing cell size. Mitotic chromosomes also decrease in size during development, presumably to scale coordinately with mitotic spindles, but underlying mechanisms are unclear. Here we combine in vivo and in vitro approaches using eggs and embryos from the frog Xenopus laevis to show that mitotic chromosome scaling is mechanistically distinct from other forms of subcellular scaling. We found that mitotic chromosomes scale continuously with cell, spindle and nuclear size in vivo. However, unlike for spindles and nuclei, mitotic chromosome size cannot be re-set by cytoplasmic factors from earlier developmental stages. In vitro, increasing nuclear-cytoplasmic (N/C) ratio is sufficient to recapitulate mitotic chromosome scaling, but not nuclear or spindle scaling, through differential loading of maternal factors during interphase. An additional pathway involving importin a scales mitotic chromosomes to cell surface area/volume ratio (SA/V) during metaphase. Finally, single-chromosome immunofluorescence and Hi-C data suggest that mitotic chromosomes shrink during embryogenesis through decreased recruitment of condensin I, resulting in major rearrangements of DNA loop architecture to accommodate the same amount of DNA on a shorter axis. Together, our findings demonstrate how mitotic chromosome size is set by spatially and temporally distinct developmental cues in the early embryo.

Data availability

Sequencing data have been deposited in GEO under the code GSE217111.

The following data sets were generated

Article and author information

Author details

  1. Coral Y Zhou

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    coral.zhou@berkeley.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7471-4645

  2. Bastiaan Dekker

    Department of Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.

  3. Ziyuan Liu

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  4. Hilda Cabrera

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  5. Joel Ryan

    Advanced BioImaging Facility, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.

  6. Job Dekker

    Department of Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    Job Dekker, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5631-0698

  7. Rebecca Heald

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    bheald@berkeley.edu
    Competing interests
    No competing interests declared.

Funding

National Institute of General Medical Sciences (R35GM118183)

  • Rebecca Heald

Jane Coffin Childs Memorial Fund for Medical Research

  • Coral Y Zhou

Howard Hughes Medical Institute

  • Job Dekker

National Human Genome Research Institute (HG003143)

  • Job Dekker

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was conducted within the guidelines for Care and Use of Laboratory Animals by the National Institutes of Health. All procedures were performed in accordance with our Animal Utilization Protocol (AUP-2014-08-6596-2) and under strict regulation by the UC-Berkeley Institutional Animal Care and Use Committee (IACUC, NIH Insurance #A4107-01).

Copyright

© 2023, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Coral Y Zhou
  2. Bastiaan Dekker
  3. Ziyuan Liu
  4. Hilda Cabrera
  5. Joel Ryan
  6. Job Dekker
  7. Rebecca Heald
(2023)
Mitotic chromosomes scale to nuclear-cytoplasmic ratio and cell size in Xenopus
eLife 12:e84360.
https://doi.org/10.7554/eLife.84360

Share this article

https://doi.org/10.7554/eLife.84360

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